Treatment of Chronic Hepatitis B Virus Infection Using Small Molecule Modulators of Nucleocapsid Assembly: Recent Advances and Perspectives

On the basis of the recent advance of basic research on molecular biology of hepatitis B virus (HBV) infection, novel antiviral drugs targeting various steps of the HBV life cycle have been developed in recent years. HBV nucleocapsid assembly is now recognized as a hot target for anti-HBV drug development. Structural and functional analysis of HBV nucleocapsid allowed rational design and improvement of small molecules with the ability to interact with the components of HBV nucleocapsid and modulate the viral nucleocapsid assembly process. Prototypes of small molecule modulators targeting HBV nucleocapsid assembly are being preclinically tested or have moved forward in clinical trials, with promising results. This Review summarizes the recent advances in the approach to develop antiviral drugs based on the modulation of HBV nucleocapsid assembly. The antiviral mechanisms of small molecule modulators beyond the capsid formation and the potential implications will be discussed.